Interactions of diet, macronutrient metabolism, and body weight change in humans

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After several days of eating a weight-maintenance diet, 20 obese adult volunteers (BMI between 30 - 40 kg/m2) will be admitted to the metabolic clinical research unit (MCRU) and, after 5 additional days of the baseline diet, their diets will be modified to result in either 85% reduction of the baseline dietary fat or a 60% reduction of the baseline dietary carbohydrate for the next 6 days. These diet modifications produce an equivalent caloric reduction. The primary outcome measurements will be changes of metabolism, brain reward circuitry and regional brain activity in response to food stimuli measured during the baseline and reduced calorie diet phases. Immediately following each controlled diet, we will measure 3 days of ad-libitum food intake using a computerized vending machine system. The subjects will return to the MCRU after a 2-10 week washout period to receive the opposite reduced calorie diet. Twenty control subjects with normal body weight (BMI between 18.5 - 25 kg/m2) will have measurements of brain reward circuitry and regional brain activity in response to food stimuli while on a balanced, weight-maintenance diet. Immediately following the second in-patient visit, all of the obese subjects will be assigned to a 12 week out-patient weight loss program with the goal of achieving at least 5% weight loss. We will investigate the relationship between short-term fat imbalances measured during the inpatient phases, and the body weight and fat changes during the weight loss program. Finally, we will evaluate the effects of weight loss on metabolism, brain reward circuitry, and regional brain activity in response to food stimuli. This study will result in an improved understanding of the physiological mechanisms that sense and respond to negative energy balance, both acutely and after several weeks, and may eventually lead to increased long-term success of obesity treatment.